1. Field of the Invention
The present invention relates to a novel pharmaceutical triterpenoids from Ilex pubescens exhibiting antithrombotic activity on humans and mammals and a conversion method of the triterpenoids from Ilex pubescens which have non-effective antithrombotic activity into the triterpenoids which have effective antithrombotic activity.
A mechanism of a platelet agglutination has been examined by the studies on the thromboxane A.sub.2 (TXA.sub.2) and prostacycline I.sub.2 (PGI.sub.2). The platelet agglutination is accelerated by TXA.sub.2 released from platelet. On the other hand, the platelet agglutination is inhibited by PGI.sub.2 released from the blood vessel. Namely, TXA.sub.2 and PGI.sub.2 are antagonized each other to maintain the homeostasis of the vascular system (B. Samuelsson, M. Goldyne, E. Granstrom, M. Hamberg, S. Hammarstrom, Malmsten, Prostaglandins and thromboxanes, Ann. Rev. Biochem. 47, 99(1978). The platelet agglutination acts an important role in the geriatric diseases; cardiovascular disease, thromboangitis obliterans, coronary disease, cerebral thrombosis, hypercholesteremia, etc.
The present invention was performed the bleeding time measurement of rats after each one of Ilex pubescens, curcumae rhizoma, Cnidii rhizoma, Angelica koreana Maximowicz, Angelicae dahuricae radix, Salvia miltriorrhiza Bunge carthami flos and Aralia cordata Thunberg was orally administered.
The above herb medicines are all related to the "blood" in chinese medicine. As a result, only the Ilex pubescens prolongs the bleeding time. Therefore, the antithrombotic compositions of the Ilex pubescens is examined.
2. Description of the Prior Art
The root of Ilex pubescens Hook. et Arn. (Aquifoliaceae), mao-dong-quing, is widely used in china for the treatment of cardiovascular disease, thromboangitis obliterans, coronary disease, cerebral thrombosis, hypercholesteremia, etc. ("Directory of Chinese Materia Medica", (Zhong Yao Da Ci Dian) ed. by Jiangsu New Medical College, Shanghai Scientific and Technological Publisher, Shanghai, p441 (1977)). The root is known to contain flavonoid glycosides (Zhang, X., Ke, M. and Ou, F.: Extraction and isolation of total flavonoid glycosides of Mao Dong Quing (Ilex pubescens) bark. Ahongcaovao, 12, 399 (1981); C. A. 96, 196519a(1982) and Xu, J. and Cheng, B.: Reaction between ammonium hydroxide-calcium chloride and flavones and its application. Zhongcaoyao, 13, 502 (1982); C. A. 98, 157840v (1983)) and ilexolide A (3-O-D-xylofuranosyl 18-dehydro-30-epiursolic acid (Zeng, L. M., Su, J. Y. and Zhang, S.: chemical structure of ilexolide A.: C. A. 101, 226825p (1984)). These compounds are reported to be active principles of the plant.